Dual acting polymeric nano-aggregates for liver cancer therapy

Al Shakarchi, Wejdan and Alsuraifi, Ali and Curtis, Anthony and Hoskins, Clare (2018) Dual acting polymeric nano-aggregates for liver cancer therapy. Pharmaceutics, 10 (2). 63. ISSN 1999-4923 (https://doi.org/10.3390/pharmaceutics10020063)

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Liver cancer treatments are often hindered by poor drug physicochemical properties, hence there is a need for improvement in order to increase patient survival and outlook. Combination therapies have been studied in order to evaluate whether increased overall efficacy can be achieved. This study reports the combined treatment of liver cancer cells with a combination treatment of chemotherapeutic agent paclitaxel and pro-apoptotic protein cytochrome C. In order to administer both agents in a single formulation, a poly(allylamine)-based amphiphile has been fabricated with the incorporation of a hybrid iron oxide-gold nanoparticle into its structure. Here, the insoluble paclitaxel becomes incorporated into the hydrophobic core of the self-assemblies formed in an aqueous environment (256 nm), while the cytochrome C attaches irreversibly onto the hybrid nanoparticle surface via gold-thiol dative covalent binding. The self-assemblies were capable of solubilising up to 0.698 mg/mL of paclitaxel (700-fold improvement) with 0.012 mg/mL of cytochrome C also attached onto the hybrid iron oxide-gold nanoparticles (HNPs) within the hydrophobic core. The formulation was tested on a panel of liver cancer cells and cytotoxicity was measured. The findings suggested that indeed a significant improvement in combined therapy (33-fold) was observed when compared with free drug, which was double the enhancement observed after polymer encapsulation without the cytochrome C in hepatocellular carcinoma (Huh-7D12) cells. Most excitingly, the polymeric nanoparticles did result in improved cellular toxicity in human endothelian liver cancer (SK-hep1) cells, which proved completely resistant to the free drug.